Materials and Methods: Our study population included 100 patients of
T2DM attending the medical out patient department of a Tertiary care center
in Kochi. Presence of fatty liver in these patients was determined by abdominal
sonography. Insulin Resistance was assessed by Homeostasis Model Assistant
– Insulin Resistance (HOMA–IR). P–value less than 0.05 was considered
statistically significant.

Results: The study group (n = 100) was divided into a NAFLD group
(n = 45) and a non–NAFLD group (n = 55). The prevalence of NAFLD in our
study was 45%. The prevalence of obesity (measured by BMI), central obesity
(measured by waist circumference and waist hip ratio) was higher in NAFLD
group with increased values of HbA1c and triglyceride levels. Insulin Resistance
was significantly higher in NAFLD group than Non NAFLD group (P value 0.02,
0.02).

Conclusion: The prevalence of NAFLD is high in patients of Type 2 DM.
Presence of NAFLD among T2DM patients is significantly associated with
Insulin resistance.

Keywords: NAFLD; Insulin Resistance; Type 2 diabetes mellitus

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a pandemic
worldwide. NAFLD denotes a spectrum of changes occurring in the
liver of non–alcoholic individuals. It is an emerging chronic liver
disease [1]. Macrovesicular hepatic steatosis is the characteristic
histological finding. NAFLD co–exists with features of the metabolic
syndrome including obesity, type 2 diabetes mellitus [T2DM],
dyslipidemia and hypertension. Hyperinsulinemia and increased free
fatty acid delivery to the liver contributes to the pathophysiology of
NAFLD [2]. NAFLD in T2DM increases the rates of cirrhosis and
mortality and hence have a poor prognosis [3].

Materials and Methods

Our study was carried out in the Departments of Internal
Medicine and Family Medicine, VPS Lakeshore Hospital, Kochi
from January 2015 to October 2016. Initial screening was carried out
to include/exclude the patients based on history taking and clinical
examination. A total of 100 patients with age more than 18 years were
included who were having diabetes of minimum 1–year duration.
Patients who consumed alcohol, patients with other liver diseases
such as malignancies, hepatitis, liver abscesses, and patients with
deranged hepatic functions due to any other febrile illnesses/disease
were excluded from the study.

Homeostasis Model Assistant–Insulin Resistance (HOMAIR)
was calculated as measure of insulin resistance using following
formula:

HOMA–IR= [fasting insulin (μU/ml) ×fasting glucose
(mmol/l)]/22.5

Presence of fatty liver was determined by abdominal
ultrasonography findings (diffuse increase in echogenicity as
compared to that of the spleen or renal cortex). Patients were
categorized as those with NALFD and those without NALFD.
Statistical analysis was carried out for study parameters between the
two groups (NAFLD and non–NAFLD) using student’s t–test. P <
0.05 was considered significant.

Results

The mean age of the patient was 55.02 years. Out of 100 patients, 47 (47%) were males and 53 (53%) were females. None of the subjects
had history of alcohol consumption. Of 100 patients with T2DM, 55
(55%) were found to have changes of fatty liver disease in abdominal
ultrasonography examination. 32 males (32%) and 33 females (33%)
had fatty liver disease. Elevated ALT (>40 IU/dl) was seen in 10
patients (10%) while 5 patients (5%) had AST >40 IU/dl (Table 1).
Mean BMI was 28.12 kg/m² (17.2–37.05) (Table 1). BMI, waist/hip
ratio, S. triglyceride level were significantly high (Table 2) in NAFLD
group as compared to Non–NAFLD group (P = 0.009, 0.0002, 0.003,
respectively). Quantitative measures of insulin resistance – S. fasting
insulin, HOMA–IR score showed significant association of NAFLD
with increased insulin resistance.

Discussion

In our study, 55% of Type 2 diabetes mellitus had NAFLD based
on abdominal ultrasound examination. This correlates with other
studies that have reported the prevalence of NAFLD among DM
patients at approximately 50% (range: 21–78%) [4]. No significant
differences in sex distribution were noted. This is in contrast to
previous studies where the prevalence of NAFLD among women was
found to be higher than men. In recent studies, it has been suggested
that both sexes might be afflicted equally [5].

BMI was significantly higher in patients with NAFLD (28.17
± 3.77) than those without NAFLD (25.19 ± 4.02) [P = 0.007].
Association of Obesity with NAFLD has been reported in various
other studies [5]. Waist/hip ratio was significantly different between
the two groups (P = 0.003). It denotes abdominal fat distribution.
In 1993, Kral et al. observed significant correlation between waist/
hip ratio and the degree of hepatic steatosis, in patients with normal
BMI [6]. Fatty liver and visceral fat are responsible for adiposityrelated
to the pathogenesis of Insulin Resistance [7]. Organ-specific
deposition of fat is a strong predictor of hyperinsulinemia and/or
insulin resistance. Increased intra-myocellular triglyceride content
correlates with muscle insulin resistance analogous to fat in the liver.
Intra-myocellular triglyceride content is assessed via muscle biopsy
or magnetic resonance imaging/computed tomography.

Transaminase levels did not show statistically significant
relationship between the NAFLD and non-NAFLD groups (P = 0.07
and 0.09 for AST and ALT, respectively). In 2005, Adams LA et al
suggested normal transaminases in up to 78% of NAFLD patients
at any time, even when complete histological findings are present
[8], explaining a poor correlation between transaminase levels and
disease severity.

Mean cholesterol, HDL, and LDL levels did show significant
difference between the two groups. Mean triglyceride levels showed
statistically significant correlation with the presence of NAFLD
(P = 0.02). As stated by previous studies on NAFLD, 20–92% of
patients diagnosed with NAFLD have hyperlipidemia [4], including
hypertriglyceridemia, hypercholesterolemia or both [5]. In 2000,
Assy N et al. described hyperlipidemia in almost 50% of the
patients who had NAFLD on ultrasound evaluations, of which only
hypertriglyceridemia and not hypercholesterolemia was shown to
pose a risk of developing liver fatty disease [9]. In 2002, Saadeh S et al.
concluded that hypertriglyceridemia along with diabetes and obesity
increases the risk of NAFLD development [10].

Glycemic control in terms of fasting glucose as well as HbA1C in
NAFLD patients were not statistically significant as compared to non-
NAFLD (P = 0.08 and 0.31 respectively). This observation suggests
a non-causal relationship between glycemic control and fatty liver.
When the triglyceride storing capacity of the fat cell is exceeded, fat
overflows to other tissues like muscle and liver. This intracellular
triglyceride metabolism interferes with insulin signaling, glucose
transport and glycogen synthesis in muscle and increases hepatic
gluconeogenesis.

Our patients in the NAFLD group had a higher prevalence of
Insulin resistance as measured by S. fasting insulin and HOMA-IR;
as compared to non-NAFLD group (P - 0.03 and 0.029, respectively).
Hyperinsulinemia itself may trigger hepatic fat deposition. This is
empirically demonstrated by the hepatic steatosis occurring under
the capsule of livers in patients undergoing peritoneal dialysis [11]
where insulin is routinely added to the dialysate.

NAFLD can be treated targeting obesity, insulin resistance,
hyperlipidemia, and hypertension [12]. NAFLD in our study was
not confirmed by liver biopsy, and this is a major limitation of our
study. Only liver biopsy can assess the severity of damage and the
prognosis of NAFLD. Ultrasonography is by far the most common
method of diagnosing NAFLD in clinical practice. In 1991, Joseph AE
et al concluded that ultrasonography has a very good sensitivity and
specificity in detecting moderate and severe steatosis in patients with
the biopsy-proven disease [13].

Conclusion

Early screening of NAFLD is advocated in regard to high incidence
of NAFLD in T2DM patients. Moreover, our study correlates insulin
resistance with the presence of NAFLD in diabetics. Large cohort
studies are necessary to validate our results.